This center will study the potential role of astrocytes as mediators of extracellular environment in the early stages following brain injury. The center will also develop clinical indices of cerebrovascular pathophysiology which will be useful in the valuation of therapies. Also, an attempt will be made to demonstrate a cause and effect relationship between specific aspects of astroglial function and cerebral blood flow regulation abnormalities following injury. Projects are: 1) "Release of cytotoxins and vasoactive agents from astrocytes." This project will test the hypothesis that blockage of anion transport inhibits swelling of astrocytes and/or release of excitotoxins from astrocytes. A second hypothesis will examine the effect of ethanol on astrocytes. A third hypothesis will involve adenosine, H+, and K+ release from astrocytes. 2) "Mechanisms of injury and protection by anion channel inhibition." This project will test hypothesis concerning the mechanisms whereby anion channel inhibition ameliorates brain injury by histopathological techniques. A second hypothesis will concern the effects of ethanol levels on respiratory control after head injury. 3) "Assessment of brain oxygenation by continuous jugular venous oximetry". These clinical studies will attempt to verify new techniques for quantifying the extent of metabolism and blood flow malregulation both temporally and regionally in severely injured patients. We will determine if arterial-venous oxygen saturation differences can be used to continuously estimate cerebral oxygenation status. A goal is to establish parameters that can be used as endpoints for therapy assessment. The core will consist of an administrative office (Core Unit A), and a data center and statistical computer facility (Core Unit B). Overall goals are to establish the means for conducting clinical research on head injured patients and to develop and test specific hypotheses both in vitro and in vivo regarding the mechanisms whereby secondary injury occurs.